Immune Activation Associated with Transarterial Radioembolization for Breast Cancer Liver Metastases

Take-Away Points

• ■ Major Focus: To characterize tumor immune microenvironment changes at PET/CT in patients with breast cancer liver metastasis (BCLM) following transarterial radioembolization (TARE).

• ■ Key Results: Lower baseline peripheral cytokine and monocyte cell levels and higher tumor microenvironment PD-1+ CD4+ lymphocytes were associated with complete response (CR) to TARE.

• ■ Impact: Immunomodulating effects of TARE have important implications for using TARE in conjunction with systemic therapeutics.

TARE is a treatment option in patients with breast cancer and liver-only metastases. There are currently no reliable imaging or biochemical features to predict CR in patients.

Deipolyi et al prospectively evaluated TARE-induced changes in the tumor microenvironment in 20 women with BCLM using peripheral blood and tumor biopsy flow cytometry, immunohistochemistry, and RNA expression analysis. The authors used the Modified PET Response Criteria in Solid Tumors to assess imaging response for each hepatic area on pre- and posttreatment PET/CT scans. Four participants who died during the study period were considered nonresponders. Mean change in maximum standardized uptake value following the first lobar TARE was −68% among 17 participants with pre- and post-TARE imaging, with eight of 20 women achieving CR. Following TARE, all participants had higher peripheral levels of IL-6, IL-10, and IL-15, while the tumor microenvironment demonstrated increased lymphocyte activation gene 3 (LAG3)+ CD4+ lymphocytes, increased expression of nitric oxide synthase 2, and decreased expression of mast cells. Those with CR had lower baseline peripheral levels of IL-6, IL-10, monocytes, and myeloid-derived suppressor cells and higher intratumoral PD-1+ CD4+ lymphocytes.

These findings suggest that TARE modulates antitumor immunity in the intratumor tissue as well as in the periphery of women with BCLM, which may explain reports of immune-mediated extrahepatic response by abscopal effects. Additionally, peripheral pretreatment immune markers may be helpful in prognostication. These data serve as a starting point for additional studies investigating TARE combined with immunotherapies, especially those involving the PD-1 pathway.

Highlighted Article

• Deipolyi AR, Johnson CB, Riedl CC, et al. Prospective evaluation of immune activation associated with response to radioembolization assessed with PET/CT in women with breast cancer liver metastasis. Radiology 2022. doi: https://doi.org/10.1148/radiol.220158